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Synthesis of oligosaccharides by using solid-phase method and hybrid method of solid-phase and liquid-phase

固相法及固相与液相混合法合成低聚糖

基本信息

批准号：
15310149
负责人：
FUKASE Koichi
金额：
$ 10.11万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Efficient synthesis of oligosaccharides by using solid-phase method and hybrid method of solid-phase and liquid-phase was investigated. We previously established "Chemical Fishing" method, where desired compound having azide function is selectively fished out of the reaction mixture by using the specific reaction between solid-supported phosphine and azide. This method was applied to the solid-phase synthesis of the elicitor pentasaccharide. Synthetic study of N-linked oligosaccharide of glycoprotein was also investigated. We developed a novel method for cleavage of trichloroethoxycarbonyl(Troc) group by radical reaction using (Bu_3Sn)_2. This method was then applied to solid-phase synthesis and rendered the use of Troc group for stereocontrolled β-glucosaminilation on solid-support by using its neighboring group participation effect. Stereoselective β-mannosylation was effected by using 4,6-O-benzylidene mannnosyl N-phenyltrifluoroacetimidate as a glycosyl donor and TMSOTf as an acid catalyst(α:β=1:9). We also established α-selective sialylation by using N-phthaloyl sialic acid phenyltrifluoroacetimidate as a donor and TMSOTf as an acid catalyst.We previously reported Synthesis based on affinity separation(SAS), where desired compound having a tag moiety is rapidly separated from a reaction mixture by using specific affinity between the tag and the molecule that recognizes the tag. In the present study, we developed the new SAS method using the interaction between podand ether tag and solid-supported ammonium ion. The present method was applied to the rapid synthesis of small oligosaccharide library including Lewis X. Various partial structures and analogues of immunostimulating glycoconjugate lipopolysaccharide and peptidoglycan were synthesized in order to elucidate their biological functions.

研究了固相法和固相液相混合法高效合成低聚糖的方法。我们以前建立了“化学打捞”方法，其中通过使用固载膦和叠氮化物之间的特异性反应从反应混合物中选择性地打捞出具有叠氮化物官能团的所需化合物。将该方法应用于诱导子五糖的固相合成。本文还对糖蛋白N-连接寡糖的合成进行了研究。提出了一种利用（Bu_3Sn）_2自由基反应裂解三氯乙氧羰基（Troc）的新方法。将该方法应用于固相合成，利用Troc基团的邻基参与效应，实现了固相载体上β-氨基葡萄糖的立体控制。以4，6-O-亚苄基甘露糖基N-苯基三氟乙酰亚胺酯为糖基供体，TMSOTf为酸催化剂（α：β=1：9），进行了立体选择性β-甘露糖基化反应。我们还建立了α-选择性唾液酸化，通过使用N-邻苯二甲酰唾液酸苯基三氟乙酰亚胺酯作为供体和TMSOTf作为酸催化剂。我们以前报道了基于亲和分离（SAS）的合成，其中具有标签部分的所需化合物通过利用标签和识别标签的分子之间的特异性亲和力从反应混合物中快速分离。本研究中，我们发展了一种新的SAS方法，利用豆荚和醚标签与固载铵离子之间的相互作用。将该方法应用于包括刘易斯X在内的小分子寡糖库的快速合成。合成了具有免疫刺激活性的糖缀合物脂多糖和肽聚糖的各种部分结构和类似物，以阐明它们的生物学功能。